Erleada-ADT Combo Increases Survival of mCSPC Patients Without Affecting Quality of Life, Phase 3 Trial Shows

Adding Erleada (apalutamide) to standard androgen deprivation therapy (ADT) increases the survival and delays disease progression in men with metastatic castration-sensitive prostate cancer (mCSPC) — and does so without compromising their quality of life — a Phase 3 clinical trial shows.

Those findings were presented in the poster, “Patient-reported outcomes (PROs) from TITAN: A phase III, randomized, double-blind study of apalutamide (APA) versus placebo (PBO) added to androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC),” at the European Society for Medical Oncology (ESMO) 2019 Congress, Sept. 27–Oct. 1 in Barcelona, Spain. The results also were published in The Lancet Oncology.

Erleada, developed by Janssen, is a form of hormone therapy that is intended to prevent male hormones from sending chemical signals that stimulate cancer growth; it does so by blocking the activity of androgen receptors. ADT is a standard prostate cancer treatment that lowers the amount of male hormones in the body.

The U.S. Food and Drug Administration (FDA) recently approved Erleada for treating men with metastatic castration-sensitive prostate cancer (mCSPC) whose cancer still responded to ADT.

The decision was based on findings from the randomized, double-blind, placebo-controlled, TITAN Phase 3 clinical trial (NCT02489318).

TITAN enrolled 1,052 adult men with mCSPC who were assigned randomly to receive either Erleada (four tablets of 60 mg, once-a-day) in combination with standard ADT, or a placebo in combination with ADT, in cycles of 28 days.

Patients were included regardless of the extent of their disease, risk of progression and prior docetaxel use, and could be either newly diagnosed with mCSPC or have relapsed metastatic disease after a first diagnosis of localized disease.

The study’s primary goals were to determine patients’ overall survival and radiographic progression-free survival (defined as the time patients lived until showing visible signs of disease progression in radiographs, or dying of any cause, whichever occurred first).

Secondary goals included a series of patient-reported outcomes, such as time to pain progression, defined as the time patients lived until experiencing their first symptoms of pain, or having an aggravation of their current levels of pain (measured by the Brief Pain Inventory-Short Form, or BPI-SF).

Additional patient-reported outcomes included assessments of fatigue (measured by the Brief Fatigue Inventory, or BFI) and overall quality of life (measured by the Euro QoL health status measure, or EQ-5D-5L and the Functional Assessment of Cancer Therapy-Prostate, or FACT-P).

Previous findings from TITAN showed the study met both primary goals, with Erleada-AADT combination increasing overall survival and the time men lived without their disease worsening, compared to ADT alone.

New data from a secondary analysis of TITAN focused on patient-reported outcomes presented at the ESMO Congress. Those showed that Erleada in combination with ADT slowed the median time to worst pain intensity progression from 12.0 months to 19.1 months, even though these differences were regarded as not statistically significant.

The median time to pain interference was not reached in any of the treatment groups, indicating fewer than half of the participants in each group experienced severe pain symptoms that would interfere with their normal daily activities.

Analysis also suggested that patients who reported severe pain at the beginning of the study were more likely to experience improvements with the addition of Erleada.

FACT-P and EQ-5D-5L overall scores indicated that patients’ health-related quality of life (HRQOL) remained stable in both treatment groups throughout the trial. Safety and tolerability assessments indicated the addition of Erleada to ADT did not change patients’ overall tolerability to treatment.

“This analysis of prespecified patient-reported outcome endpoints in TITAN showed that HRQOL did not worsen with the addition of apalutamide to ADT versus placebo for a broad population of patients with metastatic castration-sensitive prostate cancer, including those with high-volume or low-volume disease, previous docetaxel use, previous treatment for localized disease, and previously or newly diagnosed disease,” the investigators wrote.

“This maintenance of HRQOL in patients who were mostly asymptomatic at baseline, taken together with the significantly improved radiographic progression-free survival and overall survival, … and tolerability reported by patients, supports the clinical benefit of apalutamide in a broad patient population with metastatic castration-sensitive prostate cancer,” they stated.